Cancer of the ovary is the second most common cancer of the female reproductive organs and the fourth most common cause of cancer deaths among American women. Because ovarian cancers are not readily detectable by diagnostic techniques (Siemens and Auersperg, 1988, J. Cellular Physiol., 134:347-356). Because diagnosis of carcinoma of the ovary is generally only possible when the disease has progressed to a late stage of development, it is one of the most lethal of the gynecological malignancies.
There is a vital need for the identification of tumor markers which can be used in the early detection of ovarian cancer, the monitoring of cancer therapies, the immunodetection of ovarian tumors, and the development of probes for potential use in immunotherapy (Cantarow et al., 1981, Int. J. Radiation Oncol. Biol. Phys., 7:1095-1098). Although a number of potential tumor markers have been evaluated including the cancer antigen 125 (Ca-125) nonspecificity of the antigens diminish their value as markers for primary ovarian cancer (Kudlacek et al., 1989, Gyn. Onc., 35:323-329; Rustin et al., 1989, J. Clin. Onc., 7:1667-1671; Sevelda et al., 1989, Am. J. Obstet. Gynecol., 161:1213-1216; Omar et al., 1989, Tumor Biol., 10:316-323).
Several monoclonal antibodies have recently been shown to react with ovarian tumor associated antigens (Kenemans et al., 1989, Eur. J. Obstet. Gynecol. Repod. Biol., 29:207-218). These antibodies do not appear to be specific to a specific type of cancer (McDuffy, 1989, Ann. Clin. Biochen., 26:379-387). Many of these antibodies recognize determinants associated with high molecular weight glycoproteins related to mucins. Additional markers such as enzymes or activated cellular oncagenes or products of these genes have also been suggested for use as ovarian cancer markers. These potential probes, however, have not been detected in the blood and hence their use is confined to analysis of tumor tissues.
The majority, e.g., 80-90%, of ovarian cancers are thought to arise from the ovarian surface of epithelium (OSE). To date, little is known about the structure and function of the cells of the ovarian surface epithelium. It is known that the surface epithelium is a highly dynamic tissue which undergoes morphogenic changes. The OSE also has significant proliferative properties, as it it must proliferate rapidly to cover the ovulatory site after ovulation of the ova. Morphological and histochemical studies suggest that the OSE has secretory, endocytotic and transport functions which are hormonally controlled (Blaustein and Lee, 1979, Oncol. 8:34-43; Nicosia and Johnson, 1983, Int. J. Gynecol. Pathol., 3:249-260; Papadaki and Beilby, 1971, J. Cell Sci., 8:445-464; Anderson et al., 1976, J. Morphol., 150:135-164).
There is a vital need for an ovarian cancer marker which can specifically detect-ovarian cancer, which marker can be used to diagnose, monitor and identify ovarian cancers and which may be used in specific immunotherapy.